Longevity Briefs: Why Do Ovaries Age So Quickly?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Human ovaries are unusual in that they age far more rapidly than other organs. Women can start to have difficulty becoming pregnant in their 30s, but the health impact of ovarian ageing goes beyond fertility. Ovarian ageing culminating in the menopause raises the risk of age related diseases such as osteoporosis (a significant decline in bone mass) and cardiovascular disease. Despite the health impact of ovarian ageing, we don’t actually know much about the biological mechanisms that underpin it. This study aimed to improve our understanding by genetically sequencing ageing ovarian tissues.

The discovery:

When comparing ovarian tissues from four 23-29 year-old and four 49-54 year-old healthy donors, researchers found that many genes known to be associated with ageing were differently expressed in younger and older ovarian cells. These changes were greater than those typically observed in other tissues, suggesting that ovarian ageing is indeed distinct from ageing elsewhere at the genetic level. Signalling by a protein called mTOR appeared to be a particularly important component of ovarian ageing. mTOR controls how cells react to the presence of nutrients, and inhibiting mTOR in mice extends their lifespan – especially in female mice.

Researchers also observed other age-related changes. Aged ovarian cells expressed higher levels of genes associated with senescence (when cells become unable to divide). There appeared to be a breakdown in molecular signalling between different cell types, which is important as egg cells need to receive signals from other cell types in order to mature properly. Most aged ovarian cells types also appeared to suffer a loss of cell identity (that is to say, distinct cell types started to look more similar to each other in terms of gene expression).

Finally, researchers used data from genome-wide association studies to identify gene variants associated with an earlier or later menopause. These included variants of the HELB gene involved in controlling the repair of damaged DNA, and the DEPTOR gene involved in regulating mTOR signalling.

The implications:

While more work will be needed, this study has built a solid foundation for understanding and eventually treating ovarian ageing. We already have a drug – rapamycin – that inhibits mTOR and has a well established safety profile in humans, making mTOR a promising target. Since this study was quite small and only covered a limited selection of ages, we will need more studies with larger sample sizes before we can think about testing such drugs.